The central goal of this research is a better understanding of the pathophysiology of stroke. The major effort is directed toward developing and implementing better methods to enable study of important physiological mechanisms. The major projects include regional cerebral blood flow by 133 Xenon inhalation in progressive stroke and during brain activation by intellectual and physical activity; perfection of a variety of electrochemical methods for measurement of local blood flow and metabolism with electrodes; use of these for study of blood flow control mechanism at different phylogenetic levels in correlation with relevant anatomical studies of cerebral vascular innervation; perfection of methodology for ultramicroelectrode measurement of pO2, flow, and pH in the normal brain, during hypoxia and ischemia and in response to drugs; application of similar electrochemical methods for intracerebral pO2 and flow in patients undergoing intracranial pressure monitoring; biochemical and biophysical study of neuronal membrane alterations during ischemia.